A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation

Nature. 1994 Apr 21;368(6473):740-3. doi: 10.1038/368740a0.


Pharmacological studies of long-term potentiation (LTP) in the hippocampus are starting to provide a molecular understanding of synaptic plastic processes which are believed to be important for learning and memory in vertebrates. In the CA1 region of the hippocampus, the synaptic activation of glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype is necessary for the induction of LTP under most experimental conditions. The synaptic activation of metabotropic glutamate receptors (mGluRs) is also needed for the induction of LTP. We now show that the role of mGluRs in the induction of LTP is fundamentally different from that of NMDA receptors. NMDA receptors initiate a molecular event that needs to be triggered each time a tetanus is delivered to induce LTP. In contrast, mGluRs activate a molecular switch which then negates the need for mGluR stimulation during the induction of LTP. This mGluR-activated switch is input-specific and can be turned off by a train of low-frequency stimulation. The molecular switch is a new feature of LTP which has fundamental consequences for our understanding of synaptic plastic mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoates / pharmacology
  • Carbazoles / pharmacology
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hippocampus / physiology
  • In Vitro Techniques
  • Indole Alkaloids
  • Long-Term Potentiation / physiology*
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism
  • Rats
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Signal Transduction


  • Benzoates
  • Carbazoles
  • Indole Alkaloids
  • Protein Kinase Inhibitors
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • alpha-methyl-4-carboxyphenylglycine
  • staurosporine aglycone
  • Protein Kinases
  • Glycine